Impact of Neoadjuvant Chemoimmunotherapy on Surgical Outcomes and Time to Radiation in Triple-Negative Breast Cancer.

BACKGROUND: We examined the association between immunotherapy-containing and standard chemotherapy regimens with treatment delays and postoperative complications in stage II-III triple-negative breast cancer. The effect of immune-related adverse events (irAEs) was compared. PATIENTS AND METHODS: We compared 139 women treated with neoadjuvant pembrolizumab plus chemotherapy (KEYNOTE-522 regimen) from August 2021 to September 2022 with 287 consecutive patients who received neoadjuvant chemotherapy alone prior to July 2021 and underwent surgery. Baseline characteristics, time to treatments, and surgical complications were compared using two-sample non-parametric tests. Linear regression evaluated association of irAEs with time to surgery and radiation. Logistic regression identified factors associated with surgical complications. RESULTS: Age, body mass index, race, American Society of Anesthesiologists (ASA) class, and mastectomy rates were similar among cohorts. No clinically relevant difference in time from end of neoadjuvant treatment to surgery was observed [KEYNOTE-522: median 32 (IQR 27, 43) days; non-KEYNOTE-522: median 31 (IQR 26, 37) days; P = 0.048]. Time to radiation did not differ (P = 0.7). A total of 26 patients (9%; non-KEYNOTE-522) versus 11 (8%; KEYNOTE-522) experienced postoperative complications (P = 0.6). In the KEYNOTE-522 cohort, 59 (43%) of 137 patients experienced 82 irAEs; 40 (68%) required treatment. Older age (P = 0.018) and ASA class 4 (P = 0.007) were associated with delays to surgery after adjusting for clinical factors. Experiencing ≥ 1 irAE was associated with delay to radiation (P = 0.029). IrAEs were not associated with surgical complications (P = 0.4). CONCLUSIONS: We observed no clinically meaningful difference between times to surgery/adjuvant radiation or postoperative complications and type of preoperative chemotherapy. IrAEs were associated with delay to adjuvant radiation but not with postoperative complications or delay to surgery.

Bilateral Diffuse Pseudoangiomatous Stromal Hyperplasia Necessitating Mastectomy.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon, benign breast lesion often diagnosed incidentally and frequently mistaken for fibroadenoma given similar radiographic appearance. Histopathology classically reveals diffuse, dense fibrous stromal background with a complex network of spindle cells forming slit-like spaces, giving it the appearance of angiomatous proliferation. Surgical excision is generally not necessary. Here we present two unusual cases of PASH: an adolescent patient with bilateral rapid onset of symptoms, and a premenopausal patient with bilateral, diffuse, recurrent PASH. Both required mastectomy. We aim to highlight the variable nature of presentation and briefly review current management options.

Impact of the COVID-19 Pandemic on Breast Cancer Screening and Operative Treatment.

INTRODUCTION: The COVID-19 pandemic has impacted many areas of health care and had a significant impact on care delivery, including breast cancer. METHODS: To better understand the changes to detection and treatment of breast cancer at our institution, we analyzed mammogram rates (screening and diagnostic) and breast cancer operations in 2019-2020. Mammography rates were calculated using county level census data for eligible women (Z-test). For breast cancer staging, a stage severity score was analyzed with a Mann-Whitney U-test (two-tail, P < .05) with proportions derived from WFBH operative volume quarterly reports. Results: Data revealed a relative decline from 2019 to 2020 in breast cancer screening. Screening mammograms decreased by 44% or 1558 fewer screening mammograms (Z = 4.75, P < .00001) and by 21% or 771 fewer for diagnostic mammograms (Z = 2.16, P = .03). With regards to breast cancer operations, we did not identify a statistically significant difference in number of new breast cancer operations at WFBH with 340 cases in 2020 as compared to 384 cases in 2019 (P = .9905). We compared a breast cancer severity score (weighted by stage at time of operation), which did not reveal statistically significant difference in clinical stage of breast cancer at time of operation (P = .71, U = 28). CONCLUSION: Mammography was impacted more than breast surgery cases by the COVID-19 pandemic. More data needs to be collected to evaluate future morbidity and mortality related to breast cancer operations and persistent disparities related to delay in breast cancer care due to COVID-19.

Primary Breast Neuroendocrine Tumor.

Breast primary neuroendocrine tumors (BNETs) are rare, making up less than 1% of all breast carcinoma diagnosis. Their detection relies on physical exams and mammography. Diagnosis of primary BNET requires findings of no other source of neuroendocrine tumor (eg, pancreatic, lung, and appendix). Histopathologically, they typically stain positive for chromogranin A and/or synaptophysin, as do most neuroendocrine tumors. Currently, there are no agreed upon and standardized treatment protocols as it is a rare diagnosis. Treatment protocols are often built on anecdotal evidence and small case reports and series. Here we discuss a case of BNET in a 51-year-old female and discuss commonly encountered treatment protocols.

Breast Reconstruction and Nipple-Sparing Mastectomy: Technical Modifications and Their Outcomes Over Time at an Academic Breast Center.

BACKGROUND: Superior aesthetic outcomes can be achieved with mastectomy techniques that maximize breast envelope preservation and maintain the nipple-areolar complex. This is the impetus for the popularization of the nipple-sparing mastectomy (NSM). Nipple-sparing mastectomy is a challenging procedure due to potential ischemia of the mastectomy flap (which includes the nipple-areolar complex) and the risk of incomplete oncologic resection. We review our experience with NSM, identify technique modifications used over time, and evaluate reconstructive outcomes of NSM and its modifications. METHODS: A retrospective review of consecutive patients with NSM and breast reconstruction over an 8-year period was completed. RESULTS: Fifty-five patients underwent 95 NSMs. Indications included invasive and in situ cancer, atypical ductal hyperplasia, and risk reduction. In the first 4 years of experience, the most frequently used NSM incision was radial (lateral) whereas use of a variety of incision patterns was noted in the second 4 years. Overall NSM and breast reconstruction complication rate for the entire study period was 50.9% and included a full-thickness mastectomy skin flap necrosis/nipple necrosis rate of 8.4%. In situ cancer of the nipple was identified in 3.2% of the patients, and 1 patient had locoregional recurrence. Overall complication rate was lower in the second 4 years of experience with NSM and reconstruction. One third of the patients underwent intraoperative fluorescent angiography (FA) to assess mastectomy skin perfusion before reconstruction start. Of the patients who had FA due to perfusion concerns, more than 70% of studies demonstrated poor perfusion and 83.3% of these patients had reconstruction delayed based on these results. Immediate, implant-based reconstruction was performed most commonly. An average of 2.66 procedures were required to achieve reconstruction completion, and 92.4% of the patients who sought reconstruction achieved completion. CONCLUSIONS: At our institution, NSM use is increasing, NSM incision pattern types used are expanding, and complication rates are decreasing. Immediate, implant-based reconstruction is most commonly used in combination with NSM at our institution. Fluorescent angiography is used to assess mastectomy skin perfusion and likely limits mastectomy complication effects on reconstruction. Despite the occurrence of complications, most patients will complete the breast reconstruction process.

A clinical perspective on adipose-derived cell therapy for enhancing microvascular health and function: Implications and applications for reconstructive surgery.

Restoration of form and function requires apposition of tissues in the form of flaps to reconstitute local perfusion. Successful reconstruction relies on flap survival and its integration with the recipient bed. The flap's precariously perfused hypoxic areas undergo adaptive microvascular changes both internally and in connection with the recipient bed. A cell-mediated, coordinated response to hypoxia drives these adaptive processes, restoring a tissue's normoxic homeostasis via de novo vasculogenesis, sprouting angiogenesis, and stabilizing arterialization. As cells exert prolonged and coordinated effects on site, their use as biological agents merit translational consideration of sourcing angio-competent cells and delivering them to territories enduring microcirculatory acclimatization. Angio-competent cells abound in adipose tissue: a reliable, accessible, and expendable source of adipose-derived cells (ADC). When subject to enzymatic digestion and centrifugation, adipose tissue separates its various ADC: A subset of buoyant oil-dense adipocytes (the tissue's parenchymal component) accumulates on a supra-natant layer, whereas the mesenchymal component remains in the infra-natant sediment, containing the tissue's stromal vascular fraction (SVF), where angio-component cells abound. The SVF can be further manipulated, selected, or culture expanded into more specific stromal subsets (herein defined as adipose stromal cells, ASC). While promising clinical applications for ADC await clinical proof and regulatory authorization, basic science investigation is needed to elucidate the specific ADC mechanisms that influence microvascular growth, remodeling, and function following flap surgery. The objective of this article is to share the clinical perspectives of reconstructive plastic surgeons regarding the use of ADC-based therapies to help with flap tissue integration, revascularization, and wound healing. Specifically, the focus will be on considering the potential for ADC as therapeutic agents and how their clinical application motivates basic science opportunities.

Convergent effects of mouse Pet-1 deletion and human PET-1 variation on amygdala fear and threat processing.

Serotonin is critical for shaping the development of neural circuits regulating emotion. Pet-1 (FEV-1) is an ETS-domain transcription factor essential for differentiation and forebrain targeting of serotonin neurons. Constitutive Pet-1 knockout (KO) causes major loss of serotonin neurons and forebrain serotonin availability, and behavioral abnormalities. We phenotyped Pet-1 KO mice for fear conditioning and extinction, and on a battery of assays for anxiety- and depression-related behaviors. Morphology of Golgi-stained neurons in basolateral amygdala (BLA) and prelimbic cortex was examined. Using human imaging genetics, a common variant (rs860573) in the PET-1 (FEV) gene was tested for effects on threat-related amygdala reactivity and psychopathology in 88 Asian-ancestry subjects. Pet-1 KO mice exhibited increased acquisition and expression of fear, and elevated fear recovery following extinction, relative to wild-type (WT). BLA dendrites of Pet-1 KO mice were significantly longer than in WT. Human PET-1 variation associated with differences in amygdala threat processing and psychopathology. This novel evidence for the role of Pet-1 in fear processing and dendritic organization of amygdala neurons and in human amygdala threat processing extends a growing literature demonstrating the influence of genetic variation in the serotonin system on emotional regulation via effects on structure and function of underlying corticolimbic circuitry.